Compartmentalization established by claudin-11-based tight junctions in stria vascularis is required for hearing through generation of endocochlear potential
Compartmentalization established by claudin-11-based tight junctions in stria vascularis is required for hearing through generation of endocochlear potential
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DOI：
10.1242/jcs.01393
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Tsukita, S
中科院分区：
文献类型：
--
作者：
Kitajiri, SI;Miyamoto, T;Tsukita, S
克劳迪斯是在紧密连接（Tjs）上工作的细胞粘附分子，直接参与多细胞生物的区隔化。耳蜗有一个相当特殊的腔室，里面充满了内淋巴。这个隔室的特点是高K+浓度（约150 mM）和正耳蜗电位（约90 mV； EP），这两个条件都是耳蜗毛细胞将声刺激转化为电信号的必要条件。这些情况被认为是由血管纹引起的，它与内淋巴室相邻。血管纹本身构成一个孤立的隔室，由两个上皮屏障，边缘和基底细胞层所划分。由于基底细胞的TJs主要由claudin-11组成，因此产生claudin-11缺陷（Cld11(-/-)）小鼠时，预期这些小鼠血管纹的区隔化会受到影响。听觉脑干反应测量显示，Cld11（-/-）小鼠患有耳聋；虽然Cld11（-/-）耳蜗未见明显的大体形态畸形，但冷冻骨折复制电镜显示血管纹基底细胞中TJs消失。与此一致的是，示踪实验表明，基底细胞屏障被破坏，但边缘细胞屏障没有受到影响。重要的是，在Cld11（-/-）耳蜗的内淋巴室中，K+浓度维持在正常水平（约150 mM）左右，而EP被抑制至约30 mV。这些结果表明，血管纹室的建立，特别是基底细胞屏障的建立，通过EP的产生/维持而不是高K+浓度的内淋巴，对听力是必不可少的。
Claudius are cell adhesion molecules working at tight junctions (Tjs) that are directly involved in compartmentalization in multicellular organisms. The cochlea includes a rather peculiar compartment filled with endolymph. This compartment is characterized by high K+ concentration (similar to150 mM) and a positive endocochlear potential (similar to90 mV; EP), both indispensable conditions for cochlear hair cells to transduce acoustic stimuli to electrical signals. These conditions are thought to be generated by the stria vascularis, which is adjacent to the endolymph compartment. The stria vascularis itself constitutes an isolated compartment delineated by two epithelial barriers, marginal and basal cell layers. Because TJs of basal cells are primarily composed of claudin-11, claudin- 11 -deficient (Cld11(-/-)) mice were generated with an expectation that the compartmentalization in stria vascularis in these mice would be affected. Auditory brainstem response measurements revealed that Cld11(-/-) mice suffered from deafness; although no obvious gross morphological malformations were detected in Cld11(-/-) cochlea, freezefracture replica electron microscopy showed that TJs disappeared from basal cells of the stria vascularis. In good agreement with this, tracer experiments showed that the basal cell barrier was destroyed without affecting the marginal cell barrier. Importantly, in the endolymph compartment of Cld11(-/-) cochlea, the K+ concentration was maintained around the normal level (similar to150 mM), whereas the EP was suppressed down to similar to30 mV. These findings indicated that the establishment of the stria vascularis compartment, especially the basal cell barrier, is indispensable for hearing ability through the generation/ maintenance of EP but not of a high K+ concentration in the endolymph.